WO2004000292A1 - Composition stabilisee contenant de l'ascorbate de choline - Google Patents

Composition stabilisee contenant de l'ascorbate de choline Download PDF

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Publication number
WO2004000292A1
WO2004000292A1 PCT/EP2003/006387 EP0306387W WO2004000292A1 WO 2004000292 A1 WO2004000292 A1 WO 2004000292A1 EP 0306387 W EP0306387 W EP 0306387W WO 2004000292 A1 WO2004000292 A1 WO 2004000292A1
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Prior art keywords
choline
ascorbate
stabilizer
stabilized
mixture
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PCT/EP2003/006387
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German (de)
English (en)
Inventor
Alfred Oftring
Andreas Habich
Felicitas Guth
Original Assignee
Basf Aktiengesellschaft
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Priority to AU2003246546A priority Critical patent/AU2003246546A1/en
Publication of WO2004000292A1 publication Critical patent/WO2004000292A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/105—Aliphatic or alicyclic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/142—Amino acids; Derivatives thereof
    • A23K20/147—Polymeric derivatives, e.g. peptides or proteins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/174—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the invention relates to stabilized compositions containing choline ascorbate, processes for their production and their use in food and feed, and food and feed supplements.
  • Choline ⁇ [(H 3 C) 3 N + -CH 2 -CH 2 -OH] OH ⁇ ] ⁇ is the basic component of the phospholipids of the phosphoglyceride type and is widespread in the plant and animal kingdom. Choline acts as an important factor in biochemical processes such as methylation. Its deficiency leads to the formation of fatty liver in animals.
  • Choline is mainly used in the form of choline chloride or choline bitartrate in medicinal products against arterial calcification and liver parenchyma damage. Choline chloride is an important feed additive in animal nutrition.
  • Choline salts of organic acids e.g. the above-mentioned choline bitartrate, or choline salicylate, choline hydrogen citrate and choline ascorbate are among others. described in EP-A-0 812 821.
  • Choline ascorbate is characterized by the fact that it combines two active ingredients that are important for human and animal nutrition - choline and L-ascorbic acid (vitamin C) - in one molecule.
  • choline ascorbate A particular problem with choline ascorbate is its limited thermal and oxidative stability, which manifests itself after a certain time, among other things, through the appearance of discoloration. For example, solid choline ascorbate shows a brownish color on the surface after just a few days at 40 ° C and in the presence of atmospheric humidity. Similar undesirable discolorations are observed in choline ascorbate solutions after some time.
  • choline salts such as choline bitartrate, but also L-ascorbic acid and other salts, such as sodium ascorbate, are significantly more stable in color. Little is known about these decomposition reactions of choline ascorbate. It may be assumed that the presence of the quaternary ammonium (choline) counterion accelerates subsequent oxidative reactions in the ascorbic acid part of the molecule or that amine components released by thermal elimination also cause intensely colored secondary products of ascorbic acid.
  • choline quaternary ammonium
  • a first subject of the invention relates to stabilized compositions containing choline ascorbate, which are characterized in that they contain an effective amount of an additive which reduces the tendency to discoloration of the composition.
  • a “choline ascorbate-containing composition” in the sense of the present invention comprises all compositions which contain choline ascorbate and / or an ascorbate-containing choline salt mixture from a choline salt different from choline ascorbate with ascorbic acid and / or a salt of ascorbic acid.
  • These ascorbate-containing choline salt mixtures can in principle Choline salt and ascorbic acid or ascorbic acid salt in any molar ratio, such as 1: 3 to 3: 1 or 1: 2 to 2: 1, but essentially equimolar mixing ratios are preferred.
  • the suitability as a stabilizing additive according to the invention can be determined in a simple manner by using a choline ascorbate solution or a solution prepared from an ascorbate-containing choline salt mixture comprising a choline ascorbate different from choline ascorbate with ascorbic acid and / or an ascorbic acid salt in the presence of the stabilizing agent Tests addition on their tendency to discoloration.
  • the addition preferably comprises at least one stabilizer which causes a 50% by weight methanolic solution of choline ascorbate or one of the choline salt mixtures described above, in the presence of a certain amount of the stabilizer, such as 1% by weight, based on the total weight of the solution under standard conditions (heating to a temperature of 65 ° C over a period of 7 hours)
  • ⁇ 6.3 preferably ⁇ 5, in particular 0.05 to 3 or 0.1 to 2 and / or ii) a Hazen color number (determined in accordance with DIN-ISO 6271 or ASTM D 1045-68, ASTM D 263-49 or ASTM D 1209-69) of ⁇ 1000, preferably ⁇ 980, in particular 10 to 400 or 20 to 350 or 25 to 300.
  • the addition comprises at least one stabilizer which causes a 10% by weight aqueous-methanolic (preferably 1: 1 v / v) solution of choline ascorbate or a mixture of at least one choline salt different from choline ascorbate with ascorbic acid and / or an ascorbic acid salt in the presence of a certain amount of the stabilizer, such as. B. 1 wt .-%, based on the total weight of the solution, under standard conditions (heating to a temperature of 65 ° C, over a period of 7 hours).
  • aqueous-methanolic preferably 1: 1 v / v
  • ⁇ 2.0 preferably ⁇ 1, 5, in particular 0.05 to 1, 5 or 0.1 to 1, 0 and / or ii) a Hazen color number (determined in accordance with DIN-ISO 6271 or ASTM D 1045-68, ASTM D 263-49 or ASTM D 1209-69) of ⁇ 300, preferably ⁇ 250, in particular 10 to 150 or 20 to 100 or 25 to 50.
  • stabilizers are also suitable which have a more negative redox potential than ascorbic acid.
  • Stabilizers which can be used according to the invention are in the stabilized compositions in a proportion of approximately 0.05 to 30 mol%, preferably approximately 0.1 to 15 mol% or 0.5 to 10 mol%, in each case based on the molar content of choline ascorbate , or on a different choline salt (when using an ascorbate-containing choline salt mixture).
  • the stabilizer is preferably selected from sulfur-containing, phosphorus-containing or boron-containing compounds, carboxylic acids and carboxylic acid derivatives; Vitamins and vitamin precursors and derivatives; Natural mixtures; hydroxy or alkoxy aromatic compounds; or mixtures thereof.
  • the sulfur-containing stabilizer is selected in particular from cysteine, cystine, N-acetylcysteine, thioglycolate, glutathione, dihydroliponic acid, lipoic acid, sodium dithionite, methionine and thiourea; and optionally salts of these compounds.
  • the phosphorus-containing stabilizer is selected in particular from phosphorous and hypophosphorous acid, as well as salts thereof
  • the boron-containing stabilizer is especially phenylboronic acid and its salts
  • the stabilizing carboxylic acid or its derivative is selected in particular from uric, lactic, malic, citric and excess ascorbic acid, as well as ascorbyl palmitate;
  • suitable derivatives of carboxylic acids are salts or esters, such as, for example, d-C 18 alkyl or alkenyl esters.
  • the stabilizing vitamins, vitamin precursors and derivatives are preferably selected from alpha, beta and gamma tocopherol, tocotrienol and more water-soluble vitamin E derivatives, such as e.g. Vitamin E succinate or phosphate; carotenoids; isoflavones; Flavonoids and other naturally occurring polyphenols such as Quercetin, epigallocatechin, gallates, ellagic acid and ferulic acid.
  • a suitable stabilizing mixture of natural substances is e.g. a rosemary extract or green tea extract, such as described in Martinez-Tome, M. et al., J. Food Prot. 2001, 64 (9): 1412-9.
  • Stabilizing hydroxy- or alkoxy-aromatic compounds are selected from 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline (ethoxyquin), t-butylated hydroxytoluene and t-butylated hydroxyanisole.
  • Salts can be mentioned as examples of suitable functional derivatives of the above compounds.
  • Salts of the above stabilizers are especially alkali and alkaline earth metal salts, e.g. Sodium and potassium salts.
  • Preferred additives from the list above are S-containing species, such as in particular cysteine, N-acetylcysteine, dihydroliponic acid, glutathione or thioglycolate; and P-containing species such as hypophosphorous or phosphorous acid; as well as carboxylic acids such as ascorbic acid or its salts or esters.
  • S-containing species such as in particular cysteine, N-acetylcysteine, dihydroliponic acid, glutathione or thioglycolate
  • P-containing species such as hypophosphorous or phosphorous acid
  • carboxylic acids such as ascorbic acid or its salts or esters.
  • choline salts suitable according to the invention include: choline chloride,
  • Choline bitartrate tricholine citrate, bis-choline tartrate, bis-choline hydrogen phosphate, choline hydrogen phosphate, bis-choline hydrogen citrate, choline dihydrogen citrate, choline gluconate, choline salicylic, choline nicotinate, choline folate and choline carboxymethyl.
  • Suitable ascorbic acid salts are alkali and alkaline earth metal salts, such as sodium ascorbate.
  • Such stabilized ascorbate-containing choline salt mixtures contain at least one of the above choline salts in a proportion of about 1-50 wt .-%, such as. B. about 5 - 30 wt .-% and the ascorbic acid or its salt in a proportion of about 2 - 70 wt .-%, such as. B. about 5 to 50 wt .-%, each based on the total weight of the formulation.
  • the stabilizer is contained in a proportion of 0.05-30 mol%, preferably 0.1-15 mol% or 0.5-10 mol%, based on the molar content of choline salt.
  • the stabilized compositions according to the invention can be in solid, molten or liquid form, as a solution or dispersion, these liquid forms optionally additionally encapsulated, for. B. in gelatin capsules.
  • Another object of the invention relates to a method for producing a stabilized composition containing choline ascorbate, wherein i) solid choline ascorbate or a mixture of a solid choline salt with solid
  • Another object of the invention is the use of a stabilizer as defined above to reduce the tendency to discolour a composition containing choline ascorbate or an ascorbate-containing choline salt mixture.
  • the invention also relates to food or feed which, in addition to conventional food or feed components, contains a stabilized choline ascorbate composition as defined above in a proportion of about 0.001 to 50% by weight, such as, for. B. 0.5 to 40 wt .-% or 1 to 20 wt .-%, contain. Foods according to the invention in particular also include baby food.
  • the invention further relates to food or feed supplements which, in addition to conventional food or feed supplement ingredients, contain a stabilized choline ascorbate composition as defined above in a proportion of about 0.01 to 99.9% by weight, such as. B. 0.5 to 80 wt .-% or 5 to 50 wt .-%, contain.
  • the invention also relates to pharmaceuticals in solid, liquid or pasty form, characterized in that they contain an effective amount, such as, for example, 0.1 to 99.9% by weight, such as, for example, in a pharmaceutically acceptable carrier.
  • a final object of the invention relates to the use of a composition containing stabilized choline ascorbate as defined above for the production of food and feed as well as food and feed supplements.
  • both solid, melted and liquid compositions containing choline ascorbate can advantageously be stabilized according to the invention.
  • the working techniques required to formulate stabilized compositions are known per se from the prior art and e.g. described in Mollet, formulation technology, Verlag Wiley-VCH, Weinheim; or Hager's Handbook of Pharmaceutical Practice, Springer-Verlag, Heidelberg.
  • the present invention can be advantageously used to stabilize all choline ascorbates.
  • solutions or dispersions of choline ascorbate in any aqueous, alcoholic or aqueous-alcoholic solvent systems can be prepared in a manner known per se.
  • the choline ascorbate content can be in the range from approximately 0.01 to 90% by weight, preferably approximately 10 to 70% by weight, of the liquid composition.
  • the stabilizer (solid or liquid, optionally pre-dissolved in the same liquid phase) is added to the already prepared choline ascorbate solution or dispersion and a homogeneous, stabilized liquid mixture is prepared, which can be stored in this form or processed immediately.
  • Choline ascorbate can be melted. It is therefore possible to stir a stabilizing additive according to the above definition into a melt of this compound and, for example, subsequently to solidify the melt by cooling.
  • the stabilizer can also be used in a molten or solid state or as a heated solution or dispersion. There is also the possibility of evaporating a solution provided with the stabilizer, giving a supercooled melt, which then continues can be formulated.
  • the choline ascorbate content can be in the range from approximately 0.01 to 99% by weight, preferably approximately 50 to 95% by weight, of the solidified melt.
  • the present invention is also suitable for stabilizing solid, crystalline or amorphous choline ascorbates.
  • the present invention is preferably used to stabilize crystalline choline ascorbate.
  • a preferred crystalline choline ascorbate is described, for example, in the older DE-A-101 090 73.
  • the kristailisat described therein shows the most intense line in the 2 Röntgen X-ray
  • the choline ascorbate crystals have a purity of> 98%, preferably> 99%, particularly preferably> 99.5%.
  • This crystalline choline ascorbate is prepared by reacting ascorbic acid with trimethylamine and ethylene oxide, the reaction in the temperature range from - 20 ° C to 80 ° C, preferably -10 ° C to 40 ° C, particularly preferably in the temperature range from 0 ° C to 30 ° C is carried out.
  • the process is further characterized in that the reaction is carried out in a water-miscible organic solvent or in a mixture of water and a water-miscible organic solvent.
  • the water content in the solvent can be between 0 and 50% by weight, preferably between 0 and 10% by weight.
  • Suitable water-miscible solvents are, above all, water-miscible, thermally stable, volatile solvents containing only carbon, hydrogen and oxygen, such as alcohols, ethers, esters, ketones and acetals. Those solvents which are at least 10% water-miscible, have a boiling point below 200 ° C. and / or have less than 10 carbons are preferably used.
  • Methanol, ethanol, n-propanol, isopropanol, 1,2-butanediol-1-methyl ether, 1,2-propanediol-1-n-propyl ether, tetrahydrofuran or acetone are particularly preferably used. Methanol and ethanol are particularly preferred.
  • the molar ratio of the reactants trimethylamine: ascorbic acid: ethylene oxide is in the range from 0.9-1, 1: 0.9-1, 1: 0.9-2.0, preferably in the range from 1: 1: 1, 2, particularly preferably in the range of 1: 1: 1.05.
  • the choline ascorbate is preferably crystallized in one of the abovementioned solvents used for the reaction.
  • choline chloride with sodium ascorbate can also be used in a water-miscible organic solvent or in a mixture of water and a water-miscible organic solvent at temperatures in the range from -20 ° C. to 80 ° C., preferably -10 ° C. to 40 ° C, particularly preferably in the temperature range from 0 ° C to 30 ° C to crystalline choline ascorbate.
  • the sodium chloride formed in this way is e.g. filtered off.
  • the crystalline choline ascorbate produced in this way can be kept color-stable in the desired manner by adding at least one stabilizer according to the invention.
  • the crystalline choline ascorbate if necessary after crushing the accrued Crystals are mixed with a suitable amount of the solid or liquid stabilizer or stabilizer mixture, optionally dried, or further processed into other solid forms, such as, for example, granules, pellets, tablets.
  • Stabilized compositions according to the invention like conventional choline preparations, are used as an additive in food and feed or as an additive in food and feed supplements, e.g. Multivitamins.
  • the stabilized product according to the invention can be incorporated in the desired amount and in a manner known per se into conventional food and feed or food and feed supplements.
  • the stabilized compositions according to the invention can be present in the different, appropriate proportions.
  • the choline ascorbates stabilized according to the invention are suitable for the production of medicaments, such as in particular preparations for the treatment and / or prevention of cirrhosis of the liver or other liver diseases.
  • medicaments such as in particular preparations for the treatment and / or prevention of cirrhosis of the liver or other liver diseases.
  • Other potential areas of application include: improving cognitive functions; Treatment and / or prevention of various forms of dementia or Alzheimer's disease; as well as other neurodegenerative diseases; and lowering plasma homocysteine levels and the associated prevention of cardiovascular disease.
  • Dietary supplements can also be used for the purpose according to the invention.
  • compositions according to the invention for the treatment of an individual can be produced in a manner known per se.
  • the stabilized choline ascorbate is usually administered in the form of pharmaceutical compositions which comprise a pharmaceutically acceptable excipient with at least one stabilized choline ascorbate according to the invention and optionally further active ingredients.
  • These compositions can be used, for example, on oral, rectal, transdermal, sublingual, buccal, sub- cutaneous, intravenous, intramuscular or intranasal route.
  • suitable pharmaceutical formulations are solid pharmaceutical forms, such as powders, powders, granules, tablets, troches, sachets, cachets, dragees, film-coated tablets, capsules such as hard and soft gelatin capsules, suppositories or vaginal pharmaceutical forms, semi-solid pharmaceutical forms such as ointments, creams, hydrogels, pastes or plasters, and liquid pharmaceutical forms, such as solutions, emulsions, in particular oil-in-water emulsions, suspensions, for example lotions, injection and infusion preparations, eye and ear drops.
  • Implanted delivery devices can also be used to administer inhibitors according to the invention. Liposomes, microspheres or polymer matrices can also be used.
  • stabilized choline ascorbates according to the invention are usually mixed or diluted with an excipient.
  • Excipients can be solid, semi-solid or liquid materials that serve as vehicles, carriers or media for the active ingredient.
  • Suitable excipients include, for example, lactose, dextrose, succrose, sorbitol, mannitol, starches, acacia, calcium phosphate, alginates, tragacanth, gelatin, highly disperse silicon dioxide, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone and its derivatives, cellulose and its derivatives, water, alcohol Water mixtures, syrups and methyl cellulose.
  • the formulations can be pharmaceutically acceptable carriers or customary auxiliaries, such as lubricants, for example tallow, magnesium stearate, oils of vegetable origin and mineral oil; Wetting agents; emulsifying and suspending agents; preservatives such as methyl and propyl hydroxybenzoates; antioxidants; Antiirritatives; chelating agents; coating aids; Emulsion stabilizers film formers; gelling agents; Odor masking agents; masking flavors; resins; Hydrocolloids; Solvents; Solubilizing agents; Neutralizing agents; permeation; pigments; quaternary ammonium compounds; Refatting and overfatting agents; Ointment, cream or oil base materials; Silicone derivatives; spreading aids; stabilizers; Sterilanzien; Fundamentals of the suppository; Tablet excipients such as binders, fillers, lubricants, disintegrants or coatings; Propellant; Desiccant; Opacifiers; Flow regulators, thicken, thick
  • a relevant design is based on professional knowledge, such as in Fiedler, HP, Lexicon of auxiliary substances for pharmacy, cosmetics and related areas, 4th edition, Aulendorf: ECV-Editio-Kantor-Verlag, 1996, or Hager's Handbuch der Pharmaceutical Practice, Springer Verlag, Heidelberg is shown.
  • the excipients can be used individually or in a mixture.
  • Example 1 Determination of the stability of choline compounds in solution
  • Solid choline ascorbate is first prepared in a manner known per se according to DE-A-101 090 73. 0.2 mol of trimethylamine in methanol (25% by weight) was admixed with 0.2 mol of ascorbic acid while cooling to 0 ° C. 0.2 mol of ethylene oxide was gassed into this mixture in such a way that the reaction temperature did not exceed 0-5 ° C. After the end of the reaction, the reactor was flushed with nitrogen and further stirred at a temperature between 0 and 5 ° C. The choline ascorbate formed crystallized out of the reaction mixture, was filtered off, washed with methanol and recrystallized again in methanol for further purification.
  • the degree of discoloration is determined using the Gardner color number (DIN-ISO 4630) or Hazen (DIN-ISO 6271).
  • test results illustrate the surprisingly high instability of unstabilized choline ascorbate compared to other choline compounds or ascorbic acid, the instability of which was already known.
  • the stabilizing effect of the respective additive is observed by determining the color number, as described in Example 1.
  • the stabilizer not only makes choline ascorbate but also mixtures of other choline salts with ascorbic acid significantly more stable in color.
  • Formulation auxiliaries prepared in a conventional manner.
  • Example 6 Formulation example - B group vitamin tablet
  • Vitamin B 6 100 mg

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Abstract

L'invention concerne des compositions stabilisées contenant de l'ascorbate de choline, caractérisées en ce qu'elles contiennent une quantité efficace d'un additif réduisant leur tendance à la décoloration. L'invention concerne également un procédé pour la production de ces compositions stabilisées, ainsi que leur utilisation dans des aliments pour l'homme ou les animaux, dans des compléments alimentaires pour l'homme ou les animaux ou dans des médicaments.
PCT/EP2003/006387 2002-06-21 2003-06-17 Composition stabilisee contenant de l'ascorbate de choline WO2004000292A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003246546A AU2003246546A1 (en) 2002-06-21 2003-06-17 Composition comprising stabilised choline ascorbate

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10227793.1 2002-06-21
DE10227793A DE10227793A1 (de) 2002-06-21 2002-06-21 Stabilisierte Cholinascorbat enthaltende Zusammensetzung

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004028525A1 (fr) * 2002-09-24 2004-04-08 Basf Aktiengesellschaft Formulations d'ascorbate de choline
CN109125288A (zh) * 2017-06-13 2019-01-04 天津大学 一种具有炎症靶向性的多功能制剂及其制备方法和应用

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB713779A (en) * 1950-12-29 1954-08-18 Monsanto Chemicals Improvements in or relating to choline chloride compositions and feed compositions containing said choline chloride compositions
US2823166A (en) * 1954-11-17 1958-02-11 Walter H Hoffman Choline ascorbate, methods for producing same, and compositions thereof
GB932942A (en) * 1960-11-03 1963-07-31 Ashe Chemical Ltd Improvements in or relating to the production of a choline derivative
DE2222902A1 (de) * 1971-07-26 1973-02-08 Mundipharma Ag Stabilisierte cholin-salicylatverbindung
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JPS5524137A (en) * 1978-08-11 1980-02-21 Yotsukaichi Gosei Kk Treatment of choline chloride
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PATENT ABSTRACTS OF JAPAN *

Cited By (2)

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Publication number Priority date Publication date Assignee Title
WO2004028525A1 (fr) * 2002-09-24 2004-04-08 Basf Aktiengesellschaft Formulations d'ascorbate de choline
CN109125288A (zh) * 2017-06-13 2019-01-04 天津大学 一种具有炎症靶向性的多功能制剂及其制备方法和应用

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